title: Inactivation of MuxABC-OpmB transporter system in Pseudomonas aeruginosa leads to increased ampicillin and carbenicillin resistance and decreased virulence.
abstract: Resistance-Nodulation-Cell Division (RND) pumps play important roles in bacterial resistance to antibiotics. Pseudomonas aeruginosa is an important human pathogen which exhibits high level resistance to antibiotics. There are total of 12 RND pumps present in the P. aeruginosa PAOl genome. The recently characterized MuxABC-OpmB system has been shown to play a role in resistance to novobiocin, aztreonam, macrolides, and tetracycline in a multiple knockout mutation. In this study, we examined the expression levels of all the 12 RND pump gene clusters and tested the involvement of MuxABC-OpmB in pathogenicity. The results indicated that in addition to the four known constitutively expressed RND pumps, mexAB-oprM, mexGHI-opmD, mexVW, and mexXY, relatively high levels of expression were observed with mexJK and muxABC-opmB in the conditions tested. Inactivation of muxA in the muxABC-opmB operon resulted in elevated resistance to ampicillin and carbenicillin. The mutant also showed attenuated virulence in both Brassica rapa pekinensis and Drosophila melanogaster infection models. The decreased virulence at least in part was due to decreased twitching motility in the mutant. These results indicate that the RND pump MuxABC-OpmB is associated with ampicillin and carbenicillin susceptibility and also involved in pathogenesis in P. aeruginosa.
authors.affiliation: Molecular Microbiology Laboratory, Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences, Northwest University, Shaanxi, 710069, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Yang
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Lixin
authors.initials: L
authors.lastname: Shen
authors.forename: Michael
authors.initials: M
authors.lastname: Surette
authors.forename: Kangmin
authors.initials: K
authors.lastname: Duan
mesh_terms: D000667:Ampicillin / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D029741:Brassica rapa / Q000382:microbiology; D002228:Carbenicillin / Q000494:pharmacology; D004195:Disease Models, Animal; D004331:Drosophila melanogaster / Q000382:microbiology; D017353:Gene Deletion; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D010935:Plant Diseases / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity*; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*; D018440:beta-Lactam Resistance
chemical_list: D000900:Anti-Bacterial Agents; D026901:Membrane Transport Proteins; D037521:Virulence Factors; D000667:Ampicillin; D002228:Carbenicillin